abstract：:Background This Phase 1b study aimed to determine the recommended Phase 2 dose of LY2334737, an oral pro-drug of gemcitabine, in combination with capecitabine, an oral pro-drug of 5-fluorouracil, in patients with advanced solid tumors. In addition, pharmacokinetics (PK) and tumor response were evaluated. Patients and ...

journal_title：Investigational new drugs

authors： Infante JR,Benhadji KA,Dy GK,Fetterly G,Ma WW,Bendell J,Callies S,Adjei AA

更新日期：2015-04-01 00:00:00

abstract：BACKGROUND:Docetaxel-prednisone (DP) is an approved therapy for metastatic castration-resistant prostate cancer (mCRPC). Orteronel (TAK-700) is an investigational, selective, non-steroidal inhibitor of 17,20-lyase, a key enzyme in androgenic hormone production. This phase 1/2 study evaluated orteronel plus DP in mCRPC ...

journal_title：Investigational new drugs

authors： Petrylak DP,Gandhi JG,Clark WR,Heath E,Lin J,Oh WK,Agus DB,Carthon B,Moran S,Kong N,Suri A,Bargfrede M,Liu G

更新日期：2015-04-01 00:00:00

abstract：PURPOSE:Preclinical data indicate that combination HER2-directed and anti-VEGF therapy may bypass resistance to trastuzumab. A phase I trial was performed to assess safety, activity, and correlates. EXPERIMENTAL DESIGN:Patients with advanced, refractory malignancy were enrolled (modified 3 + 3 design with expansions f...

journal_title：Investigational new drugs

authors： Falchook GS,Moulder S,Naing A,Wheler JJ,Hong DS,Piha-Paul SA,Tsimberidou AM,Fu S,Zinner R,Janku F,Jiang Y,Huang M,Parkhurst KL,Kurzrock R

更新日期：2015-02-01 00:00:00

abstract：:VEGF signaling through VEGFR-2 is the major factor in glioblastoma angiogenesis. CT-322, a pegylated protein engineered from the 10th type III human fibronectin domain, binds the VEGFR-2 extracellular domain with high specificity and affinity to block VEGF-induced VEGFR-2 signaling. This study evaluated CT-322 in an o...

journal_title：Investigational new drugs

authors： Schiff D,Kesari S,de Groot J,Mikkelsen T,Drappatz J,Coyle T,Fichtel L,Silver B,Walters I,Reardon D

更新日期：2015-02-01 00:00:00

abstract：:Ergot alkaloids are psychoactive and vasoconstricting agents of the fungus Claviceps purpurea causing poisoning such as ergotism in medieval times (St. Anthony's Fire). This class of substances also inhibits tumor growth in vitro and in vivo, though the underlying mechanisms are unclear as yet. We investigated six erg...

journal_title：Investigational new drugs

authors： Mrusek M,Seo EJ,Greten HJ,Simon M,Efferth T

更新日期：2015-02-01 00:00:00

abstract：INTRODUCTION:Continuous efforts from scientists of diverse fields are necessary not only to better understand the mechanism by which multidrug resistant (MDR) cancer cells occur, but also to boost the discovery of new cytotoxic compounds. This work was designed to assess the cytotoxicity and the mechanism of action of ...

journal_title：Investigational new drugs

authors： Kuete V,Sandjo LP,Djeussi DE,Zeino M,Kwamou GM,Ngadjui B,Efferth T

更新日期：2014-12-01 00:00:00

abstract：:Drug discovery involves various steps and is a long process being even more demanding for complex diseases such as cancer. Tumors are ensembles of subpopulations with different mutations, require very specific and effective strategies. Conventional drug screening technologies may not be adequate and efficient anymore....

journal_title：Investigational new drugs

authors： Kadioglu O,Efferth T

更新日期：2014-12-01 00:00:00

abstract：:The poor prognosis of children with high-grade glioma (HGG) and high-risk neuroblastoma, despite multidisciplinary therapeutic approaches, demands new treatments for these indications. F14512 is a topoisomerase II inhibitor containing a spermine moiety that facilitates selective uptake by tumor cells via the Polyamine...

journal_title：Investigational new drugs

authors： Leblond P,Boulet E,Bal-Mahieu C,Pillon A,Kruczynski A,Guilbaud N,Bailly C,Sarrazin T,Lartigau E,Lansiaux A,Meignan S

更新日期：2014-10-01 00:00:00

abstract：BACKGROUND:ASP9521 is a first-in-class orally available inhibitor of the enzyme 17 β-hydroxysteroid dehydrogenase type 5 (17 βHSD5; AKR1C3), catalysing the conversion of dehydroepiandrosterone and androstenedione into 5-androstenediol and testosterone. It has demonstrated anti-tumour activity in in vitro and in vivo pr...

journal_title：Investigational new drugs

authors： Loriot Y,Fizazi K,Jones RJ,Van den Brande J,Molife RL,Omlin A,James ND,Baskin-Bey E,Heeringa M,Baron B,Holtkamp GM,Ouatas T,De Bono JS

更新日期：2014-10-01 00:00:00

abstract：:Bcl-2 family proteins are the key regulators of the intrinsic apoptotic pathway, controlling the point-of no-return and setting the threshold to engage the death machinery in response to chemical damage. Bcl-2 proteins have emerged as attractive targets for anti-cancer drug development. Navitoclax is a selective, pote...

journal_title：Investigational new drugs

authors： Vlahovic G,Karantza V,Wang D,Cosgrove D,Rudersdorf N,Yang J,Xiong H,Busman T,Mabry M

更新日期：2014-10-01 00:00:00

abstract：PURPOSE:To investigate the safety, optimal dosing, pharmacokinetics and clinical activity of a regimen of navitoclax (ABT-263) combined with gemcitabine in patients with solid tumors. EXPERIMENTAL DESIGN:Patients with solid tumors for which gemcitabine was deemed an appropriate therapy were enrolled into one of two di...

journal_title：Investigational new drugs

authors： Cleary JM,Lima CM,Hurwitz HI,Montero AJ,Franklin C,Yang J,Graham A,Busman T,Mabry M,Holen K,Shapiro GI,Uronis H

更新日期：2014-10-01 00:00:00

abstract：:Monoclonal antibodies directed against the immune checkpoint protein cytotoxic T-lymphocyte antigen-4 (CTLA-4; CD152) have been investigated in metastatic melanoma and other cancers and have shown promising results. Inhibition of CTLA-4 characteristically induces well-known side effects called "immune-related adverse ...

journal_title：Investigational new drugs

authors： Izzedine H,Gueutin V,Gharbi C,Mateus C,Robert C,Routier E,Thomas M,Baumelou A,Rouvier P

更新日期：2014-08-01 00:00:00

abstract：:The novel oral antiangiogenic agent TSU-68 was investigated in patients with metastatic breast cancer. Patients with anthracycline-pretreated metastatic breast cancer were randomly assigned to receive either TSU-68 400 mg twice daily on days 1-21 plus docetaxel 60 mg/m(2) on day 1 every 3 weeks, or docetaxel 60 mg/m(2...

journal_title：Investigational new drugs

authors： Kim SB,Yoo C,Ro J,Im SA,Im YH,Kim JH,Ahn JH,Jung KH,Song HS,Kang SY,Park HS,Chung HC

更新日期：2014-08-01 00:00:00

abstract：:SHetA2 is a small molecule flexible heteroarotinoid (Flex-Het) with promising cancer prevention and therapeutic activity. Extensive preclinical testing documented lack of SHetA2 toxicity at doses 25 to 150 fold above effective doses. Knowledge of the SHetA2 molecular target(s) that mediate(s) the mechanism of SHetA2 a...

journal_title：Investigational new drugs

authors： Benbrook DM,Nammalwar B,Long A,Matsumoto H,Singh A,Bunce RA,Berlin KD

更新日期：2014-06-01 00:00:00

abstract：AIM:To quantify the effect of food on the systemic exposure of lapatinib at steady state when administered 1 h before and after meals, and to observe the safety and tolerability of lapatinib under these conditions in patients with advanced solid tumours. METHODS:This was a three-treatment, randomised, three-sequence c...

journal_title：Investigational new drugs

authors： Devriese LA,Koch KM,Mergui-Roelvink M,Matthys GM,Ma WW,Robidoux A,Stephenson JJ,Chu QS,Orford KW,Cartee L,Botbyl J,Arya N,Schellens JH

更新日期：2014-06-01 00:00:00

abstract：BACKGROUND:This phase I, dose-finding study evaluated the maximum tolerated dose (MTD), safety, pharmacokinetics, and antitumor activity of sunitinib plus S-1/cisplatin in Japanese patients with advanced/metastatic gastric cancer. PATIENTS AND METHODS:Patients received oral sunitinib on a continuous daily dosing (CDD)...

journal_title：Investigational new drugs

authors： Boku N,Muro K,Machida N,Hashigaki S,Kimura N,Suzuki M,Lechuga M,Miyata Y

更新日期：2014-04-01 00:00:00

abstract：:A phase I trial of first-line vorinostat, an orally bio-available histone deacetylase inhibitor, in combination with capecitabine plus cisplatin (XP) was performed to assess recommend phase II trial dose in patients with advanced gastric cancer. Five dose levels of three-weekly vorinostat-XP were tested; vorinostat wa...

journal_title：Investigational new drugs

authors： Yoo C,Ryu MH,Na YS,Ryoo BY,Lee CW,Maeng J,Kim SY,Koo DH,Park I,Kang YK

更新日期：2014-04-01 00:00:00

abstract：BACKGROUND:We performed a phase I study to determine the dose and safety of everolimus as a combination chemotherapy in peripheral T-cell lymphoma (PTCL). METHODS:Four dose levels (2.5 to 10 mg) of everolimus from days 1 to 14 with CHOP (750 mg/m(2) cyclophosphamide, 50 mg/m(2) doxorubicin, and 1.4 mg/m(2) (maximum 2 ...

journal_title：Investigational new drugs

authors： Kim SJ,Kang HJ,Kim JS,Eom HS,Huh J,Ko YH,Lee J,Yim DS,Lee SY,Park WS,Yang WI,Lee SS,Suh C,Kim WS

更新日期：2013-12-01 00:00:00

abstract：:Epidermal growth factor receptor (EGFR) gene mutations activate the KRAS-RAF-MEK-ERK pathway in lung cancer cells. EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib induce apoptosis of cancer cells, but prolonged treatment is often associated with acquired resistance. Here, we identified a novel MEK1/2 inhibito...

journal_title：Investigational new drugs

authors： Song JY,Kim CS,Lee JH,Jang SJ,Lee SW,Hwang JJ,Lim C,Lee G,Seo J,Cho SY,Choi J

更新日期：2013-12-01 00:00:00

abstract：:We explored whether barasertib (AZD1152), a selective Aurora B kinase inhibitor, is a substrate for P-glycoprotein (Pgp, MDR1), breast cancer resistance protein (BCRP), and multidrug resistance protein 2 (MRP2) in vitro. Cell survival, drug transport, and competition experiments with barasertib pro-drug and the more a...

journal_title：Investigational new drugs

authors： Marchetti S,Pluim D,van Eijndhoven M,van Tellingen O,Mazzanti R,Beijnen JH,Schellens JH

更新日期：2013-10-01 00:00:00

abstract：:Glioblastoma (GBM), one of the most malignant human neoplasias, responds poorly to current treatment modalities, with temozolomide (TMZ) being the drug most frequently used for its treatment. Tetra-O-methyl Nordihydroguaiaretic Acid (M4N) is a global transcriptional repressor of genes dependent on the Sp1 transcriptio...

journal_title：Investigational new drugs

authors： Castro-Gamero AM,Borges KS,Moreno DA,Suazo VK,Fujinami MM,de Paula Gomes Queiroz R,de Oliveira HF,Carlotti CG Jr,Scrideli CA,Tone LG

更新日期：2013-08-01 00:00:00

abstract：:Survivin is expressed in tumor cells, including acute myeloid leukemia (AML), regulates mitosis, and prevents tumor cell death. The antisense oligonucleotide sodium LY2181308 (LY2181308) inhibits survivin expression and may cause cell cycle arrest and restore apoptosis in AML. In this study, the safety, pharmacokineti...

journal_title：Investigational new drugs

authors： Erba HP,Sayar H,Juckett M,Lahn M,Andre V,Callies S,Schmidt S,Kadam S,Brandt JT,Van Bockstaele D,Andreeff M

更新日期：2013-08-01 00:00:00

abstract：:CP-4126 is a gemcitabine (2',2'-difluorodeoxycytidine; dFdC) 5' elaidic acid ester. The purpose of this dose-escalating study was to assess safety, pharmacokinetics (PK) and preliminary antitumor activity of the oral formulation and to determine the recommended dose (RD) for phase II studies. The study had a two-step ...

journal_title：Investigational new drugs

authors： Stuurman FE,Voest EE,Awada A,Witteveen PO,Bergeland T,Hals PA,Rasch W,Schellens JH,Hendlisz A

更新日期：2013-08-01 00:00:00

abstract：BACKGROUND:To evaluate the safety and tolerability of two different weekly doses of the fully humanized epidermal growth factor receptor (EGFR)-targeting monoclonal antibody matuzumab combined with high-dose 5-fluorouracil, leucovorin and cisplatin (PLF) in the first-line treatment of patients with EGFR-positive advanc...

journal_title：Investigational new drugs

authors： Trarbach T,Przyborek M,Schleucher N,Heeger S,Lüpfert C,Vanhoefer U

更新日期：2013-06-01 00:00:00

abstract：:BMS-754807 is an inhibitor of insulin-like growth factor-1 receptor (IGF-1R) and insulin receptor that also represses aurora kinase. Cancers that express high levels of IGF-1/IGF-1R are sensitive to BMS-754807; however, it shows limited efficacy in non-small cell lung cancer (NSCLC) in which IGF-1R-driven signals may ...

journal_title：Investigational new drugs

authors： Lee SJ,Kim EJ,Lee HJ,Kim SY,Oh SJ,Ryu JS,Moon DH,Ahn JH,Kim SW

更新日期：2013-06-01 00:00:00

abstract：:Withaferin A (WA), a steroidal lactone derived from the plant Vassobia breviflora, has been reported to have anti-proliferative, pro-apoptotic, and anti-angiogenic properties against cancer growth. In this study, we identified several key underlying mechanisms of anticancer action of WA in glioblastoma cells. WA was f...

journal_title：Investigational new drugs

authors： Grogan PT,Sleder KD,Samadi AK,Zhang H,Timmermann BN,Cohen MS

更新日期：2013-06-01 00:00:00

abstract：:Chaetoglobosin K (ChK) is a natural product that inhibits anchorage-dependent and anchorage-independent growth of ras-transformed cells, prevents tumor-promoter disruption of cell-cell communication, and reduces Akt activation in tumorigenic cells. This study demonstrates how ChK modulates the JNK pathway in ras-trans...

journal_title：Investigational new drugs

authors： Ali A,Sidorova TS,Matesic DF

更新日期：2013-06-01 00:00:00

abstract：PURPOSE:This study investigated the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), and pharmacokinetic (PK) profiles of DHP107, a novel oral paclitaxel containing neither Cremophor EL nor P-glycoprotein (P-gp) inhibitor. PATIENTS AND METHODS:Patients with advanced solid tumors refractory to all standard t...

journal_title：Investigational new drugs

authors： Hong YS,Kim KP,Lim HS,Bae KS,Ryu MH,Lee JL,Chang HM,Kang YK,Kim H,Kim TW

更新日期：2013-06-01 00:00:00

abstract：:Major discrepancies concerning risk-benefit assessments and regulatory actions are frequent among regulatory agencies. We explored the differences by scrutinizing a case of gemtuzumab ozogamicin (GO) in patients with acute myeloid leukaemia (AML). Assessment reports of GO were retrieved form the websites of the US Foo...

journal_title：Investigational new drugs

authors： Tanimoto T,Tsubokura M,Mori J,Pietrek M,Ono S,Kami M

更新日期：2013-04-01 00:00:00

abstract：BACKGROUND:Foretinib is a small-molecule, oral multikinase inhibitor primarily targeting the mesenchymal epithelial transition (MET) factor receptor, and the vascular endothelial growth factor receptor 2. We conducted a phase II study to evaluate the single-agent activity and tolerability of foretinib in patients with ...

journal_title：Investigational new drugs

authors： Seiwert T,Sarantopoulos J,Kallender H,McCallum S,Keer HN,Blumenschein G Jr

更新日期：2013-04-01 00:00:00

abstract：OBJECTIVE:The anti-vascular endothelial growth factor (VEGF) antibody bevacizumab has received considerable attention as a first-line treatment of advanced colorectal cancers. Difficulties associated with effectively monitoring the activity of this drug have prompted us to seek a pharmacodynamic marker suitable for def...

journal_title：Investigational new drugs

authors： Shin SJ,Hwang JW,Ahn JB,Rha SY,Roh JK,Chung HC

更新日期：2013-02-01 00:00:00

abstract：BACKGROUND:Hepatocellular carcinoma (HCC) cells are auxotrophic for arginine, depletion of which leads to tumour regression. The current study evaluated safety, pharmacokinetics (PK)/ pharmacodynamics (PD) parameters, and potential anti-tumor activity of pegylated recombinant human arginase 1 (peg-rhArg1) in advanced H...

journal_title：Investigational new drugs

authors： Yau T,Cheng PN,Chan P,Chan W,Chen L,Yuen J,Pang R,Fan ST,Poon RT

更新日期：2013-02-01 00:00:00

abstract：:This study was designed to test the hypothesis that specific inhibition of cathepsins B and L will cause death of neuroblastoma cells. Five compounds that differ in mode and rate of inhibition of these two enzymes were all shown to cause neuroblastoma cell death. Efficacy of the different compounds was related to thei...

journal_title：Investigational new drugs

authors： Cartledge DM,Colella R,Glazewski L,Lu G,Mason RW

更新日期：2013-02-01 00:00:00

abstract：PURPOSE:This phase I study aims at assessing the safety and tolerability of LY2603618, a selective inhibitor of Checkpoint Kinase 1, in combination with pemetrexed and determining the maximum tolerable dose and the pharmacokinetic parameters. EXPERIMENTAL DESIGN:This was an open-label, multicenter, dose-escalation stu...

journal_title：Investigational new drugs

authors： Weiss GJ,Donehower RC,Iyengar T,Ramanathan RK,Lewandowski K,Westin E,Hurt K,Hynes SM,Anthony SP,McKane S

更新日期：2013-02-01 00:00:00

abstract：:We have recently developed a liposomal nanoparticle (LNP) formulation of irinotecan based on loading method that involves formation of a complex between copper and the water soluble camptothecin. The loading methodology developed for irinotecan was evaluated to develop a LNP topotecan formulation (referred to herein a...

journal_title：Investigational new drugs

authors： Patankar NA,Waterhouse D,Strutt D,Anantha M,Bally MB

更新日期：2013-02-01 00:00:00

abstract：INTRODUCTION:This multicenter, open-label, phase II study was carried out to compare the efficacy and safety of cilengitide (EMD 121974), a selective inhibitor of the cell-surface integrins αVβ3 and αVβ5, with that of docetaxel in patients with advanced non-small-cell lung cancer (NSCLC). METHODS:Patients (n = 140) wi...

journal_title：Investigational new drugs

authors： Manegold C,Vansteenkiste J,Cardenal F,Schuette W,Woll PJ,Ulsperger E,Kerber A,Eckmayr J,von Pawel J

更新日期：2013-02-01 00:00:00

abstract：:PA-U2, an engineered anthrax protective antigen that is activated by urokinase was combined with wildtype lethal factor in the treatment of Colo205 colon adenocarcinoma in vitro and B16-BL6 mouse melanoma in vitro and in vivo. This therapy was also tested in combination with the small molecule paclitaxel, based on pri...

journal_title：Investigational new drugs

authors： Wein AN,Liu S,Zhang Y,McKenzie AT,Leppla SH

更新日期：2013-02-01 00:00:00

abstract：:Breast cancer is commonly treated with anti-estrogens or aromatase inhibitors, but resistant disease eventually develops and new therapies for such resistance are of great interest. We have previously isolated several tamoxifen-resistant variant sub-lines of the MCF-7 breast cancer cell line and provided evidence that...

journal_title：Investigational new drugs

authors： Leung E,Rewcastle GW,Joseph WR,Rosengren RJ,Larsen L,Baguley BC

更新日期：2012-12-01 00:00:00

abstract：:The neurotransmitter serotonin is involved in numerous bodily functions via seven different serotonin receptor subfamilies. Serotonin plays a role in gastrointestinal functions like intestinal secretion or peristalsis and neuropsychiatric events like depression or migraine. One of these subtypes has been found on glio...

journal_title：Investigational new drugs

authors： Sturzu A,Sheikh S,Klose U,Echner H,Kalbacher H,Deeg M,Nägele T,Horger M,Ernemann U,Heckl S

更新日期：2012-12-01 00:00:00

abstract：BACKGROUND:Dacomitinib (PF-00299804) is an oral, irreversible, small molecule inhibitor of human epidermal growth factor receptor-1, -2, and -4 tyrosine kinases. METHODS:This phase I, open-label, dose-escalation study (clinicaltrials.gov: NCT00783328) primarily evaluated the safety and tolerability of dacomitinib by d...

journal_title：Investigational new drugs

authors： Takahashi T,Boku N,Murakami H,Naito T,Tsuya A,Nakamura Y,Ono A,Machida N,Yamazaki K,Watanabe J,Ruiz-Garcia A,Imai K,Ohki E,Yamamoto N

更新日期：2012-12-01 00:00:00